Background: The recurrent human rhinovirus (HRV) infection in early life is associated with asthma development. We hypothesized that repetitive HRV infection increases susceptibility to asthma by training an aberrantly amplified innate immune response in airway epithelial cells.

Methods: Primary normal human bronchial epithelial (NHBE) and asthmatic human bronchial epithelial (DHBE) cells were cultured at the air-liquid interface (ALI). They were infected with HRV-16 three (repetitive infection), two or one time, and then exposed to IL-13. RT-PCR was performed to quantify intracellular HRV-16 viral content over the period of repetitive infection. At the end of experiment, inflammatory factors were measured at gene and protein levels by RT-PCR and MSD U-PLEX Platform, respectively.

Results: The HRV-16 viral load in NHBEs and DHBEs peaked 24 hours after each infection and then gradually decreased to the initial level prior the next infection. In both NHBEs and DHBEs, co-stimulation of HRV-16 infection (repetitive/twice/once) and IL-13 enhanced the expression of RIG-1, IL-8 and IL-4 genes in comparison with controls or IL-13 treatment alone. Moreover, repetitive HRV-16 infection followed by IL-13 induced the highest expression level of these genes compared to any other treatment. In line with this, the highest protein production level of IL-8, IP-10, IFNβ, IFN?1, IL-4, IL-5 and IL-10 was induced by co-stimulation of repetitive HRV-16 infection and IL-13 treatment, in NHBEs and DHBEs.

Conclusion: The results indicate that recurrent HRV-16 infection of airway epithelium could pave the way to exacerbate IL-13 induced airway inflammation but demands further epigenetic studies.